@ Herbal Cascara Sagrada (Rhamnus purshiana)

Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.

The ingredients
Beside the main compound of anthraquinones, otyher compounds include anthraquinone glycosides, (emodin, frangulin, iso-emodin, aloe-emodin, and chrysophanol), rhein, aloin, malic acid, tannic acid, cascarosides A, B, C, and D, and hydroxy anthracene derivatives (HAD), etc.

1. Cascara Sagrada and Metabolic syndrome
Metabolic syndrome
According to the American Academy of Family Physicians, insulin resistance often goes along with other health problems, such as diabetes, high cholesterol and high blood pressure. These problems are all risk factors for heart disease. When a person has many of these problems at the same time, doctors commonly call it “metabolic syndrome.” It is sometimes called “insulin resistance syndrome” or “syndrome X.” Many people who have type 2 diabetes also have metabolic syndrome
Other defined it as a disorder of energy utilization and storage, diagnosed by a co-occurrence of 3 out of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density cholesterol (HDL) levels. The metabolic syndrome increases the risk of developing cardiovascular disease, particularly heart failure, and diabetes.
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.

The Benefits
Emodin, a chemical compound found in Cascara Sagrada may pocess the potential to treat matabolic syndrome by inhibiting 11beta-HSD1 activity of liver and fat significantly and reversing prednisone-induced insulin resistance in mice. Scientific evidence to support the above, including Dr. Wang and the research team in the study in ob/ob mice indicated that emodin (30 μmol/L) suppressed 11-dehydrocorticosterone-induced adipogenesis without affecting corticosterone-induced adipogenesis; emodin (3 μmol/L) reduced 11-dehydrocorticosterone-stimulated lipolysis, but had no effect on corticosterone-induced lipolysis. Moreover, emodin (3 μmol/L) partly reversed the impaired insulin-stimulated glucose uptake and adiponectin secretion induced by 11-dehydrocorticosterone but not those induced by corticosterone. In ob/ob mice, long-term emodin administration decreased 11β-HSD1 activity in mesenteric adipose tissues, lowered non-fasting and fasting blood glucose levels, and improved glucose tolerance. Other in the study of  Glucocorticoid excess (Cushing's syndrome)  causes metabolic syndrome showed that a selective 11β-HSD1 inhibitor, KR-67183, may provide a new therapeutic window in the prevention and treatment without toxicity in type 2 diabetes with obesity as KR-67183 concentration-dependently inhibited 11β-HSD1 activity in human and mouse 11β-HSD1 over-expressed cells and in the ex vivo assay of C57BL/6 mice and he administration of KR-67183 (20 and 50mg/kg/day, orally for 28 days) improved the glucose tolerance and insulin sensitivity with suppressed 11β-HSD1 activity in the liver and fat.

References
1. Metabolic syndrome (Wikipedia)
2.  Metabolic syndrome, (American Academy of Family Physicians)
3. Cascara sagrada (Rhamnus purshiana)(Sigma Aldrich)
4. "Emodin, a natural product, selectively inhibits 11beta-hydroxysteroid dehydrogenase type 1 and ameliorates metabolic disorder in diet-induced obese mice" by Feng Y, Huang SL, Dou W, Zhang S, Chen JH, Shen Y, Shen JH, Leng Y.(PubMed)
5. Emodin, an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, regulates adipocyte function in vitro and exerts anti-diabetic effect in ob/ob mice. by Wang YJ, Huang SL, Feng Y, Ning MM, Leng Y.
6. Anti-diabetic and anti-adipogenic effects of a novel selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor in the diet-induced obese mice. by Park JS, Rhee SD, Jung WH, Kang NS, Kim HY, Kang SK, Ahn JH, Kim KY.(PubMed)
7. [Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada].[Article in Danish]" by Jacobsen C, Semb S, Kromann-Andersen H(PubMed)
8. "Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity" by Nadir A, Reddy D, Van Thiel DH.(PubMed)
9. "Occupational respiratory allergic disease induced by Passiflora alata and Rhamnus purshiana" by Giavina-Bianchi PF Jr, Castro FF, Machado ML, Duarte AJ.(PubMed)

2. Cascara Sagrada and pancreatic cancer
Cancer of pancreas or pancreatic cancer is defined as condition of a malignant neoplasm of the pancreas, as the cells have become cancerous and divided uncontrollably. Most pancreatic cancers start in the ducts (exocrine component of the pancreas) that carry pancreatic juices with cancer of an epithelium that originates in glandular tissue accounts for over 75 - 90% of all cases of exocrine cancers.

The benefits
Emodin, the major components of Cascara Sagrada (Rhamnus purshiana), has been found to be effective on inducing the apoptosis of pancreatic cancer cells and inhibiting tumor growth through in cellular responses to stimuli (nuclear factor kappa-light-chain-enhancer of activated B cells) and the results suggested that it may contain potential anti-tumor effect on pancreatic cancer as its promotion of apoptosis and suppression of angiogenesis and be considered as potential agent for prevention and treatment of pancreatic cancer. Others in the study of  emodin in the inhibition of XIAP and NF-κB, showed emodin enhances the antitumor effect of gemcitabine in SW1990 pancreatic cancer may be via the downregulation of NF-κB expression, thus inhibiting the expression of XIAP.

References
1. Antitumor activity of emodin against pancreatic cancer depends on its dual role: promotion of apoptosis and suppression of angiogenesis by Lin SZ, Wei WT, Chen H, Chen KJ, Tong HF, Wang ZH, Ni ZL, Liu HB, Guo HC, Liu DL.(PubMed)
2. Enhanced antitumor efficacy by the combination of emodin and gemcitabine against human pancreatic cancer cells via downregulation of the expression of XIAP in vitro and in vivo by Wang ZH, Chen H, Guo HC, Tong HF, Liu JX, Wei WT, Tan W, Ni ZL, Liu HB, Lin SZ.(PubMed)
3. [Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada].[Article in Danish]" by Jacobsen C, Semb S, Kromann-Andersen H(PubMed)
4. "Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity" by Nadir A, Reddy D, Van Thiel DH.(PubMed)
5. "Occupational respiratory allergic disease induced by Passiflora alata and Rhamnus purshiana" by Giavina-Bianchi PF Jr, Castro FF, Machado ML, Duarte AJ.(PubMed)


3. Cascara Sagrada and cancer
Cancer is a class of diseases in which a group of cells growing and multiplying disordered and uncontrollable way in our body, have become progressively worse and damaged other healthy tissues, sometimes spreads to other organs in the body via lymph or blood and results may be in death.

The benefits
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an anthraquinone derivative originally isolated from Rheum officinale Baill known in research community for decades to possess anticancer properties. In the study to examine the effects of emodin on P2X7R(The adenosine 5'-triphosphate (ATP)-gated Ca(2+)-permeable channel P2X7 receptor )-dependent Ca(2+) signaling, extracellular matrix degradation, showed that emodin inhibits human cancer cell invasiveness by specifically antagonizing the P2X7R. Others in the evaluation of natural anthracene-derived compounds as antimitotic agents, showed that  anthraquinones possess promising anti-mitotic activity and may have the potential to be lead compounds for the development of a new class of multifaceted natural anticancer/antimitotic agents.

References
1. Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors.

Jelassi B, Anchelin M, Chamouton J, Cayuela ML, Clarysse L, Li J, Goré J, Jiang LH, Roger S.(PubMed)

2. Evaluation of natural anthracene-derived compounds as antimitotic agents by Badria FA, Ibrahim AS.(PubMed)
3. [Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada].[Article in Danish]" by Jacobsen C, Semb S, Kromann-Andersen H(PubMed)
4. "Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity" by Nadir A, Reddy D, Van Thiel DH.(PubMed)
5. "Occupational respiratory allergic disease induced by Passiflora alata and Rhamnus purshiana" by Giavina-Bianchi PF Jr, Castro FF, Machado ML, Duarte AJ.(PubMed)

4. Cascara Sagrada and Breast cancer
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.

The benefits
Emodin, a chemical component found in Cascara Sagrada, an anthraquinone derivative has been found to possess anti cancer activity by induced cell apotoposis. in the study of the effects of emodin on Multi-drug resistance to chemotherapeutic agents is a major cause of treatment failure in breast cancer. In this studyto evaluate the effects of emodin on reversing the multi-drug resistance, through the ERCC1 protein expression in breast cancer cell line, Emodin may effectively reverse the multi-drug resistance in MCF-7/Adr cells and down-regulate ERCC1 protein expression.

References
1. Emodin enhances cisplatin-induced cytotoxicity via down-regulation of ERCC1 and inactivation of ERK1/2. by Ko JC, Su YJ, Lin ST, Jhan JY, Ciou SC, Cheng CM, Chiu YF, Kuo YH, Tsai MS, Lin YW.(PubMed)
2. [Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada].[Article in Danish]" by Jacobsen C, Semb S, Kromann-Andersen H(PubMed)
3. "Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity" by Nadir A, Reddy D, Van Thiel DH.(PubMed)
4. "Occupational respiratory allergic disease induced by Passiflora alata and Rhamnus purshiana" by Giavina-Bianchi PF Jr, Castro FF, Machado ML, Duarte AJ.(PubMed)


5. Cascara Sagrada and non-small cell lung cancer (NSCLC)
Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.

Lung cancer is defined as a condition of the abnormal growth of the cells in the lung's tissue. Most common form of primary lung cancers are derived from epithelial cells. In Us, Lung cancer is the leading cause of cancer deaths, causing 158,683 people deaths, including 88,329 men and 70,354 women, according to 2007 statistic. Non-small cell lung cancer is the most common type of lung cancer. It usually grows and spreads methodically and predictably.Most common types of lung cancers include
a. Squamous-cell carcinoma often found in an outer area of the lung,
b. Large-cell carcinoma found in the center of the lung by an air tube
c. Adenocarcinoma found in any part of the lung.

The ingredients
Beside the main compound of anthraquinones, otyher compounds include anthraquinone glycosides, (emodin, frangulin, iso-emodin, aloe-emodin, and chrysophanol), rhein, aloin, malic acid, tannic acid, cascarosides A, B, C, and D, and hydroxy anthracene derivatives (HAD), etc.

The benefits
In last article, we have shown that Emodin, an anthraquinone derivative, may effectively reverse the multi-drug resistance in MCF-7/Adr cells and down-regulate ERCC1 protein expression. In the study of  the cytotoxic effect of combined emodin and cisplatin on NSCLC cell lines, emodin alone or combined with cisplatin significantly decreased expression of ERCC1 mRNA levels, may lead to novel therapy in the future for NSCLC. Other in study of the same also support the effects of emodin  suppressed by emodin to induce cytotoxicity in NSCLC cells by activation of the MKK1/2-ERK1/2 pathway.

The Side effects
1. Cascara Sagrada can be liver toxic.
2. It may cause Postal hypertension
Cascara sagrada (CS) has been associated with the development of cholestatic hepatitis, complicated by portal hypertension.
3. Fresh cut, dried bark may cause vomiting and diarrhea.
4. It may allergic effect.
5. Etc.

References
1. Emodin enhances cisplatin-induced cytotoxicity via down-regulation of ERCC1 and inactivation of ERK1/2 by Ko JC, Su YJ, Lin ST, Jhan JY, Ciou SC, Cheng CM, Chiu YF, Kuo YH, Tsai MS, Lin YW.(PubMed)
2. Suppression of ERCC1 and Rad51 expression through ERK1/2 inactivation is essential in emodin-mediated cytotoxicity in human non-small cell lung cancer cells by Ko JC, Su YJ, Lin ST, Jhan JY, Ciou SC, Cheng CM, Lin YW.(PubMed)
3. [Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada].[Article in Danish]" by Jacobsen C, Semb S, Kromann-Andersen H(PubMed)
4. "Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity" by Nadir A, Reddy D, Van Thiel DH.(PubMed)
5. "Occupational respiratory allergic disease induced by Passiflora alata and Rhamnus purshiana" by Giavina-Bianchi PF Jr, Castro FF, Machado ML, Duarte AJ.(PubMed)

6. Cascara Sagrada and Herpes simplex virus
Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.
Herpes is defined as a viral disease caused by both Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2).

The ingredients
Beside the main compound of anthraquinones, otyher compounds include anthraquinone glycosides, (emodin, frangulin, iso-emodin, aloe-emodin, and chrysophanol), rhein, aloin, malic acid, tannic acid, cascarosides A, B, C, and D, and hydroxy anthracene derivatives (HAD), etc.

The benefits
Anthraquinone derivatives such as emodin have recently been found to protect against deposit of  amyloid plaques and tau aggregation-induced cell death. In the study to evaluate the anti viral effects of emodin against HSV infection, emodin showed a positive result in inhibiting the replication of HSV-1 and HSV-2 in cell culture at the concentration of 50 μg/ml with antiviral index of 2.07 and 3.53, respectively as well as enhancing the survival rate of HSV-infected mice ad may be considered as a promising agent in the clinical therapy of HSV infection. Other in the study of the same indicated that emodin also inhibits the yields of HSV-1 but via the suppression of a novel target, UL12.

The Side effects
1. Cascara Sagrada can be liver toxic.
2. It may cause Postal hypertension
Cascara sagrada (CS) has been associated with the development of cholestatic hepatitis, complicated by portal hypertension.
3. Fresh cut, dried bark may cause vomiting and diarrhea.
4. It may allergic effect.
5. Etc.

References
(1) The effect of emodin, an anthraquinone derivative extracted from the roots of Rheum tanguticum, against herpes simplex virus in vitro and in vivo by Xiong HR, Luo J, Hou W, Xiao H, Yang ZQ.(PubMed)
(2) Emodin is a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures by Hsiang CY, Ho TY.(PubMed)
3. [Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada].[Article in Danish]" by Jacobsen C, Semb S, Kromann-Andersen H(PubMed)
4. "Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity" by Nadir A, Reddy D, Van Thiel DH.(PubMed)
5. "Occupational respiratory allergic disease induced by Passiflora alata and Rhamnus purshiana" by Giavina-Bianchi PF Jr, Castro FF, Machado ML, Duarte AJ.(PubMed)

7. Cascara Sagrada and RV-induced asthma
Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.
Rhinoviruses are viral infective agents in humans, associated to the cause of the common cold

The ingredients
Beside the main compound of anthraquinones, otyher compounds include anthraquinone glycosides, (emodin, frangulin, iso-emodin, aloe-emodin, and chrysophanol), rhein, aloin, malic acid, tannic acid, cascarosides A, B, C, and D, and hydroxy anthracene derivatives (HAD), etc.

The effects
Mitoxantrone, a anthraquinone derivative found in Cascara Sagrada may be the next potential agent in treating severe asthma caused the Rhinoviruses. It is known that severe asthma is associated the immune response to infection and inflammation and a family of enzymes involved in cellular functions (PI3K). In the study of the effects of Mitoxantrone allergic mice  infected with RV1B, showed an effective potential in RV-induced asthma by blocking pro-inflammatory pathways regulated by multiple cellular processes of PI3K. The effect of the herb may be more profound as the chemical constituent of emodin showed a significantly anti inflammatory activity with capable of interacting with several major inflammatory molecular targets. The result re-emphasizes its potential therapeutic role in the treatment of inflammatory diseases.

The Side effects
1. Cascara Sagrada can be liver toxic.
2. It may cause Postal hypertension
Cascara sagrada (CS) has been associated with the development of cholestatic hepatitis, complicated by portal hypertension.
3. Fresh cut, dried bark may cause vomiting and diarrhea.
4. It may allergic effect.
5. Etc.


References
(1) Targeted abrogation of diverse signal transduction cascades by emodin for the treatment of inflammatory disorders and cancer by Shrimali D, Shanmugam MK, Kumar AP, Zhang J, Tan BK, Ahn KS, Sethi G.(PubMed)
(2) Inhibiting AKT Phosphorylation Employing Non-Cytotoxic Anthraquinones Ameliorates TH2 Mediated Allergic Airways Disease and Rhinovirus Exacerbation by Cesar de Souza Alves C, Collison A, Hatchwell L, Plank M, Morten M, Foster PS, Johnston SL, França da Costa C, Vieira de Almeida M, Couto Teixeira H, Paula Ferreira A, Mattes J.(PubMed)

8. Cascara Sagrada and (Mastitis) inflammation of breast tissue
Cascara sagrada is a species of buckthorn, genus Rhamnus, belonging to the family Rhamnaceae, native to western North America, it's bark has been used in traditional medicine for gastrointestinal support. and it is thought to have a laxative and natural cleansing, etc., effect.
Mastitis is the  inflammation of breast tissue, mostly caused by Staphylococcus aureus

The ingredients
Beside the main compound of anthraquinones, otyher compounds include anthraquinone glycosides, (emodin, frangulin, iso-emodin, aloe-emodin, and chrysophanol), rhein, aloin, malic acid, tannic acid, cascarosides A, B, C, and D, and hydroxy anthracene derivatives (HAD), etc.

The effects
Nanosilver particles (AAgNPs), a derivative of chemical constituent of aloin found in Cascara Sagrada may be the protential target used as antibiotics for treatment of infectious and inflammatory diseases, including mastitis. In the Staphylococcus aureus induced murine mastitis study of a total of 40 female mice were divided into five groups of eight animals each, Nanosilver particles (AAgNPs) is found to be effective (concentration of 21.8) than antibiotic as it exerted the anti inflammatory activity in reducing white blood cell (poly-morpho nuclear cell) infiltration.Other chemical compound emodin found in the herb, in a study of of the same but with  lipopolysaccharide (LPS)-induced mastitis also found to significantly reduced infiltration of neutrophilic granulocyte. These result may be given the green light for the chemical compounds of Cascara Sagrada used as a novel treatment strategy for mastitis.

The Side effects
1. Cascara Sagrada can be liver toxic.
2. It may cause Postal hypertension
Cascara sagrada (CS) has been associated with the development of cholestatic hepatitis, complicated by portal hypertension.
3. Fresh cut, dried bark may cause vomiting and diarrhea.
4. It may allergic effect.
5. Etc.

References
(1) Emodin ameliorates lipopolysaccharide-induced mastitis in mice by inhibiting activation of NF-κB and MAPKs signal pathways by Li D, Zhang N, Cao Y, Zhang W, Su G, Sun Y, Liu Z, Li F, Liang D, Liu B, Guo M, Fu Y, Zhang X, Yang Z.(PubMed)
(2) Evaluation of therapeutic potential of nanosilver particles synthesised using aloin in experimental murine mastitis model by Chaitanya Kumar TV, Muralidhar Y, Prasad PE, Prasad TN, Alpha Raj M.(PubMed)

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